Discovery of a new way to increase the effectiveness of antibiotics against “superbugs”


This immunotherapeutic enhances the phagocytosis of human neutrophils (blue nuclear stain, Hoeschest) of S. aureus (red, pHrodo stain). Credit: (C) Dr Jennifer Payne

A multidisciplinary project led by Australian researchers at EMBL at Monash University and Harvard University has found a way to make antibiotics more effective against antibiotic-resistant bacteria, also known as “superbugs.”

Antimicrobial resistance to superbugs has evolved and is one of the top 10 global public health threats facing humanity, according to the World Health Organization.

This new research will pave the way for increasing the effectiveness of antibiotics, without clinicians having to resort to risky strategies of administering higher doses to patients or relying on the discovery of new types of antibiotics. .

During a bacterial infection, the body uses molecules called chemoattractants to recruit neutrophils to the site of infection. Neutrophils are immune cells capable of encapsulating and killing dangerous bacteria that are essential for the immune response. The researchers attached a chemotactic to an antibiotic, allowing them to improve the recruitment of immune cells and improve their capacity for destruction.

The results have now been published in Natural communications.

“When we look at how our immune system can fight bacteria, we look at two important aspects. The first is our ability to trap bacterial cells and kill them. The second is the signals – chemoattractants – calling for more neutrophils, white blood cells that direct the immune system’s response to resolve infection, ”said Dr Jennifer Payne, EMBL Australia and Monash Biomedicine principal investigator. Discovery Institute.

The researchers linked a chemotactic known as formyl peptide to vancomycin, a commonly used antibiotic that binds to the surface of the bacteria, and conducted their studies on infections with Staph aureus, one of the bacteria resistant to the bacteria. most problematic antibiotics.

“We have been working on the use of dual-function antibiotic-chemoattractant hybrids, which enhance the recruitment of neutrophils and increase the uptake and destruction of bacteria,” said Dr Payne.

“By stimulating our strong immune system in this way with the immunotherapeutic antibiotic, we have shown in mouse models that the treatment is 2 times more effective than just using the antibiotic alone at a dose that is one fifth lower,” said Associate Professor Max Cryle. , EMBL Australia group leader at the Monash Biomedicine Discovery Institute.

“This very promising new line of research brings many potential benefits to the ever-growing threat of drug-resistant superbugs,” said Associate Professor Cryle.

The project was funded by VESKI and the Sister City Melbourne Foundation who took Dr Payne across the world to Boston to learn and conduct research in microfluidics, collaborating with Associate Professor Daniel Irima and Dr Felix Ellett , Harvard experts in this field. .

“Microfluidics was revolutionary for this research, as it allowed us to generate an infection on a chip to monitor the recruitment of human immune cells and observe in real time how our immunotherapeutic enhances their ability to kill MRSA. Just like what would happen in our body, ”said Dr. Payne,

Partners are sought to continue this research in clinical trials with the potential to develop a preventive antibiotic strategy in the intensive care environment to protect our most vulnerable.

Reference: “Antibiotics-chemoattractants improve the clearance of neutrophils from Staphylococcus aureus” October 25, 2021, Nature Communication.
DOI: 10.1038 / s41467-021-26244-5

The work resulted in a patent covering immunotherapy, with intellectual property owned by Monash University.


Sara H. Byrd

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